Normal Saline Versus Lactated Ringer's Solution for Acute Pancreatitis Resuscitation

Number of participants with local complications

Presence of acute peripancreatic fluid collections, acute necrotic collection, pseudocyst, walled-off necrosis, gastric outlet dysfunction, splenic or portal vein thrombosis, and colonic necrosis according to the revised Atlanta Classification (https://doi.org/10.1136/gutjnl-2012-302779).

Time frame: From date of randomization until 30 days after randomization

Number of participants with necrotizing pancreatitis

Presence of acute necrotic collections according to the revised Atlanta Classification (https://doi.org/10.1136/gutjnl-2012-302779).

Time frame: From date of randomization until 30 days after randomization

Number of participants with infection of pancreatic collections or necrosis

Extraluminal gas in the pancreatic and/or peripancreatic tissues on CT scan or when a sample from the collection/necrosis contains pus or is positive for bacteria and/or fungi on Gram stain or culture.

Time frame: From date of randomization until 30 days after randomization

Number of participants with systemic inflammatory response syndrome

At least 2 criteria: A) pulse \>90 beats/min, B) respirations \>20/min or arterial blood PaCO2 \<32 mm Hg, C) temperature \<36°C or \>38°C, D) white blood cell count \<4,000 cells/mm3 or \>12,000 cells/mm3 or \>10% bands

Time frame: At 24 and 48 hours

Number of systemic inflammatory response syndrome criteria

The criteria are: A) pulse \>90 beats/min, B) respirations \>20/min or arterial blood PaCO2 \<32 mm Hg, C) temperature \<36°C or \>38°C, D) white blood cell count \<4,000 cells/mm3 or \>12,000 cells/mm3 or \>10% bands

Time frame: At 24 and 48 hours

PAN-PROMISE symptom scale

PAN-PROMISE scale: a 7-symptom scale patient-reported outcome (range, 0 to 10 for each symptom; overall range, 0 to 70, with higher scores indicating higher symptom intensity). Details: https://doi.org/10.1136/gutjnl-2020-320729

Time frame: At 24 and 48 hours (final value and change from baseline)

Time to oral refeeding

Days from baseline to oral refeeding

Time frame: From date of randomization until 30 days after randomization

Number of participants with invasive treatment

Any of the following: thoracocentesis due to pancreatitis-induced pleural effusion, percutaneous and/or endoscopic drainage of pancreatic or peripancreatic fluid collections or necrosis, endoscopic or surgical necrosectomy, endoscopic retrograde cholangiopancreatography due to A) ruptured common bile duct, B) jaundice caused by compression of the common bile duct, C) main pancreatic duct leakage

Time frame: From date of randomization until 30 days after randomization

Number of participants with nutritional support

Use of enteral (nasogastric or nasojejunal) or parenteral feeding

Time frame: From date of randomization until 30 days after randomization

Number of participants with intensive care unit admission

Admission in the intensive care unit

Time frame: From date of randomization until 30 days after randomization

Number of participants with exacerbation of coexisting condition

Exacerbation of pre-existing co-morbidity. The definition provided by the Revised Atlanta Classification is " Exacerbation of pre-existing co-morbidity, such as coronary artery disease or chronic lung disease, precipitated by the acute pancreatitis is defined as a systemic complication. In this document, we distinguish between persistent organ failure (the defining feature of severe acute pancreatitis) and other systemic complications, which are an exacerbation of pre-existing co-morbid disease." (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779) For the WATERLAND trial we define exacerbation of pre-existing co-morbidity as

Time frame: From date of randomization until 30 days after randomization

Number of participants with any organ failure

Definition according to the revised Atlanta classification (https://doi.org/10.1136/gutjnl-2012-302779): organ failure is defined by the presence of any of the following criteria: A) kidney failure as a creatinine ≥1.9 mg/dL or \>170 micromol/L, B) cardiovascular failure as a systolic blood pressure \<90 mmHg despite fluid resuscitation, and C) respiratory failure as a PaO2/FIO2≤300

Time frame: From date of randomization until 30 days after randomization

Number of participants with persistent organ failure

Organ failure lasting more than 48h (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)

Time frame: From date of randomization until 30 days after randomization

Number of participants with shock

Systolic blood pressure \<90 mmHg despite fluid resuscitation (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)

Time frame: From date of randomization until 30 days after randomization

Number of participants with respiratory failure

PaO2/FIO2≤300 (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)

Time frame: From date of randomization until 30 days after randomization

Number of participants with kidney failure

Creatinine ≥1.9 mg/dL or \>170 micromol/L (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)

Time frame: From date of randomization until 30 days after randomization

Mortality (number of participants)

Death

Time frame: From date of randomization until 30 days after randomization

Hospital stay

Days from recruitment to discharge from index admission

Time frame: From date of randomization until 30 days after randomization

C-reactive protein

C-reactive protein blood levels

Time frame: At 48 hours from randomization

Number of participants with hypovolemia

WATERFALL trial criteria for hypovolemia (see https://www.nejm.org/doi/10.1056/NEJMoa2202884)

Time frame: At 24 and 48 hours from randomization

Number of participants with fluid overload

WATERFALL trial criteria for fluid overload (see https://www.nejm.org/doi/10.1056/NEJMoa2202884)

Time frame: From randomization to 72 h thereafter

Number of participants with acute kidney injury

KDIGO criteria: increase in serum creatinine of ≥0.3 mg/dL within 48 hr or ≥50% within 7 days or urine output of \<0.5 mL/kg/hr for \>6 hr (https://doi.org/10.1159/000339789)

Time frame: At 24 and 48 hours from randomization

Number of participants with hyperkalemia

Venous potassium\>5mEq/L

Time frame: At 24 and 48 hours from randomization

Number of participants with hypercalcemia

Venous calcium corrected by proteins\>10.5mg/dL or 2.62 mmol/L

Time frame: At 24 and 48 hours from randomization

Number of participants with hyperchloremia

Venous chloride\>106mEq/L

Time frame: At 24 and 48 hours from randomization

Number of participants with acidosis

Venous blood pH \<7.35

Time frame: At 24 and 48 hours from randomization

Number of participants with hyperchloremic acidosis

Patients with venous chloride\>106mEq/L and venous blood pH \<7.35

Time frame: At 24 and 48 hours from randomization

Number of participants with composite safety outcome (primary safety outcome)

Fluid overload or acute kidney injury or hyperkalemia or hypercalcemia or hyperchloremia or acidosis

Time frame: At 24 and 48 hours from randomization